The present invention relates generally to a method for impregnating a porous material with a cross-linkable composition, as well as a material produced by such a method. After crosslinking, the cross-linkable composition may form a hydrogel upon exposure to a humid environment. More particularly, the present invention relates to utilizing a pressure differential to control the degree of impregnation and the placement of the composition within the porous material.
It is generally known to provide an implantable material, such as a prosthetic device, with a composition which is either coated onto, or impregnated within, the material in order to render the material impermeable to fluid. In certain applications, bioresorbable compositions are provided for this purpose. In such cases, the composition is resorbed over time and tissue ingrowth encapsulates the prosthesis. Therapeutic agents may additionally be incorporated into the composition, or added subsequently. If the material has low surface activity, application of the composition may require pretreatment of the material.
Various methods of providing compositions which may be coated onto or impregnated into implantable materials are known. It is known to coat textile grafts with a composition by contacting a graft with a composition and subsequently applying pressure, thereby impregnating the graft with the composition. For example, U.S. Pat. Nos. 5,197,977, 4,842,575, and 5,108,424 disclose the use of force to impregnate a textile graft with collagen.
U.S. Pat. No. 4,911,713, to Sauvage et al., describes a process for impregnating knit and woven textile grafts with a solution, thereby rendering the grafts fluid impermeable. The process includes the step of pretreating a graft with a crosslinking agent that reacts with a protein, resulting in a gelatin formation that will render the graft fluid-impermeable. This process allegedly fills the interstices of the textile graft with a solution by controlling gelation time.
U.S. Pat. No. 5,665,114 to Weadock discloses a method of impregnating the pores of implantable prostheses with insoluble, biocompatible, biodegradable materials of natural origin through the use of force. The disclosed method involves clamping one end of a prosthetic, filling the inner lumen of the prosthetic with a composition, and using pressure to cause migration of the composition into the interstices of the ePTFE walls.
Some compositions are so rapidly resorbed as to be of limited usefulness. Crosslinking of polymeric compositions increases their integrity and reduces their rate of resorption. For example, U.S. Pat. Nos. 5,410,016 and 5,529,914 to Hubbell et al. disclose water-soluble coating compositions which form hydrogels when crosslinked (See also, Sawhney, A. S., Pathak, D. P., Hubbell, J. A., Macromolecules 1993, 26, 581-587). Additionally, U.S. Pat. No. 5,854,382 discloses water-insoluble polymer systems for impregnation and coating which are cross-linkable to form hydrogels.
Various applications require the use of porous materials, particularly prosthetic devices, to have very specific characteristics relating to the rate of bioresorption of compositions associated with the material, the degree of fluid impermeability of the material, and the ability of the material to promote endothelial cell adhesion and proliferation and smooth muscle cell ingrowth. For example, when a porous material is less than one hundred percent impregnated with a cross-linkable composition, tissue ingrowth, such as smooth muscle cell ingrowth, is promoted. These specific characteristics will determine the suitability of a particular prosthetic device for a particular medical application.
A disadvantage of known techniques of coating and impregnating porous implantable materials is the inability to control the degree, uniformity, and placement of an impregnating composition within the pores of a porous material. Accordingly, there exists a need for a process which allows a porous material, particularly an implantable prosthetic suitable for use as a medical device, to be impregnated with a composition through the application of pressure, wherein the degree of impregnation of the material, as well as the placement of the composition within specific regions of the material, can be controlled with great precision. There further exists a need for a process which allows the composition to be crosslinked following impregnation in order to secure the composition within the pores of the porous material.
The present invention relates to a process for controllably impregnating a cross-linkable composition into the pores of a porous material, such as an expanded polytetrafluoroethylene (ePTFE) material through the use of a nonreactive gas, a vacuum, or a combination thereof. The application of gas, vacuum, or a combination of gas and vacuum allows for precise control over the degree of impregnation of the cross-linkable compositions within the pores of the material as well as precise control over the placement of the cross-linkable composition within desired regions of the porous material. The cross-linkable composition is subsequently crosslinked in situ, securing the composition within the pores of the material. The cross-linkable composition may form a hydrogel in a humid environment. The invention also relates to an impregnated implantable member produced by such a process.
In one aspect of the invention, there is provided a process which includes: a) providing a porous material having a wall defined by an inner and an outer surface; b) disposing a cross-linkable composition adjacent to, or in contact with, one of the inner or outer surfaces; c) effecting a pressure differential across the inner and outer surfaces through a pressure means selected from the group consisting of a nonreactive gas, a vacuum, or a combination thereof, wherein the pressure on the surface adjacent to or in contact with the cross-linkable composition is greater than the pressure on the surface not in contact with the cross-linkable composition, the pressure differential causing the cross-linkable composition to controllably impregnated the porous material; and d) effecting crosslinking of the cross-linkable composition within the porous material.
The process includes spacing the porous material concentrically about a mandrel to define a cavity therebetween to receive the cross-linkable composition, the mandrel comprising one or more openings for communicating the nonreactive gas, the vacuum, or the combination thereof. The process further includes the step of conducting the controlled impregnation in a pressure chamber.
In a further aspect of the invention, there is provided a process which includes: a) providing a porous material with a wall defined by an inner and an outer surface; b) disposing a cross-linkable first composition adjacent to, or in contact with, one of the inner or the outer surfaces; c) disposing a second composition adjacent to, or in contact with, the other of the inner or the outer surfaces not in contact with, or adjacent to, the first cross-linkable composition; d) effecting a first pressure differential across the wall of the porous material to cause one of the cross-linkable first composition and the second composition to impregnate the porous material by means of a nonreactive gas, a vacuum, or a combination thereof; e) effecting a second pressure differential across the wall of the porous material to cause the other of the cross-linkable first composition and the second composition to impregnate the porous material by means of a nonreactive gas, a vacuum, or a combination thereof; f) effecting crosslinking of the cross-linkable first composition within the porous material.
The process includes spacing the porous material concentrically about a mandrel, the mandrel comprising one or more openings for receiving the nonreactive gas, the vacuum, or the combination thereof, wherein the porous material and the mandrel define a cavity into which the cross-linkable composition may placed, and wherein the controlled impregnation is conducted in a pressure chamber.
The present invention further relates to impregnated implantable materials, such as medical devices. An impregnated implantable material of the present invention includes a porous material produced by the process including: a) providing a porous material having a wall defined by an inner and an outer surface; b) disposing a cross-linkable composition adjacent to, or in contact with, one of the inner or the outer surfaces; c) effecting a pressure differential across the inner and outer surfaces through a pressure means selected from the group consisting of a nonreactive gas, a vacuum, or a combination thereof, wherein the pressure on the surface adjacent to or in contact with the cross-linkable composition is greater than the pressure on the surface not in contact with the cross-linkable composition, the pressure differential causing the cross-linkable composition to controllably impregnated the porous material; and d) effecting crosslinking of the cross-linkable composition within the porous material.
In this process of producing the impregnated implantable member, the porous material is spaced concentrically about a mandrel, the mandrel comprising one or more openings for receiving the nonreactive gas, the vacuum, or the combination thereof, wherein the porous material and the mandrel define a cavity into which the cross-linkable composition may be placed.
The cross-linkable composition may be flowable and may be selected from the group consisting of polymers and copolymers. The composition may be a neat liquid, an emulsion, a liquid polymer or copolymer, or a polymer or copolymer in a solid phase. Desirably, the cross-linkable composition includes a copolymer which includes a bioresorbable region, a hydrophilic region, and a plurality of cross-linkable f unctional groups per polymer chain. Further, the copolymer may be a di-block copolymer, a tri-block copolymer, or a star copolymer.
The cross-linkable composition may be crosslinked by high energy radiation, thermal radiation, or visible light, or combinations thereof. Additionally, the composition may include a free radical initiator such as an azo compound or peroxide.
Additionally, the cross-linkable composition may include one or more bio-therapeutic agents such as thrombo-resistant agents, antibiotic agents, anti-tumor agents, cell cycle regulating agents, their homologs, derivatives, fragments, pharmaceutical salts, and combinations thereof.
The cross-linkable composition may also include one or more populations of cells, which may be transfected with a genetic construct. The cells may be able to produce and release a therapeutically useful composition.